Quorum sensing controls Vibrio cholerae multicellular aggregate formation

Bacteria communicate and collectively regulate gene expression using a process called quorum sensing (QS). QS relies on group-wide responses to signal molecules called autoinducers. Here, we show that QS activates a new program of multicellularity in <i>Vibrio cholerae</i>. This program, which we term aggregation, is distinct from the canonical surface-biofilm formation program, which QS represses. Aggregation is induced by autoinducers, occurs rapidly in cell suspensions, and does not require cell division, features strikingly dissimilar from those characteristic of <i>V. cholerae</i> biofilm formation. Extracellular DNA limits aggregate size, but is not sufficient to drive aggregation. A mutagenesis screen identifies genes required for aggregate formation, revealing proteins involved in <i>V. cholerae</i> intestinal colonization, stress response, and a protein that distinguishes the current <i>V. cholerae</i> pandemic strain from earlier pandemic strains. We suggest that QS-controlled aggregate formation is important for <i>V. cholerae</i> to successfully transit between the marine niche and the human host.